Glucagon is a polypeptide hormone, secreted by the .alpha.-cells of the pancreatic islets of Langerhans. It is a single-chain polypeptide consisting of 29 amino acids in the following sequence: ##STR1##
Glucagon is used for the treatment of hypoglycemia due to its metabolic effects. Glucagon also exerts a spasmolytic effect on smooth muscle and an inhibitory effect on gastric secretion.
Glucagon is isolated from pancreas extracts. The extraction of glucagon from pancreas from slaughtered animals is a complicated process and requires large amounts of pancreas. As glucagon is furthermore sensitive to proteolytic degradation the product from the extraction of pancreas is inhomogenous and only about 1/4 of the glucagon content of pancreas is obtained.
From EP-patent application No. 81302978 (see also Ser. No. 279,153 filed June 30, 1981 now U.S. Pat. No. 4,598,065) fragments or derivatives of glucagon are known with the following general formula: EQU R.sup.1 -R.sup.2 (II)
wherein R.sup.1 represents His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Al a-Gln-Asp, and R.sup.2 represents OH, the peptide chains -Phe-Val-Gln-Trp-Leu or -Met-Asn-Thr or a corresponding peptide chain which is identical with the two last-mentioned peptide chains with the proviso that one or more of the amino acid(s) of the said two last-mentioned peptide chains has/have been omitted.
The compounds of formula (II) possess a similar spasmolytic effect and a similar inhibitory effect on gastric acid secretion as that of glucagon, but show no or minor, negligible metabolic effect. Hence, compounds of formula (II) are considered superior to glucagon when only a spasmolytic effect or an inhibition of gastric acid secretion is desired.
The compounds of formula (II) can be prepared either from natural glucagon or by the rather troublesome methods which are generally known in peptide synthesis. A preferred compound of formula (II) is glucagon (1-21).
In this specification numbers in a paranthesis after glucagon indicate the number of amino acids. Natural glucagon contains 29 amino acids and is referred to as glucagon(1-29) (or just glucagon). Glucagon(1-21) contains the first 21 amino acid residues of naturally occurring glucagon and so on.
The object of the present invention is to provide a more profitable commercial process for the preparation of glucagon or fragments or derivatives thereof by use of recombinant DNA techniques.